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MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression post-transcriptionally. In women with polycystic ovary syndrome (PCOS), several miRNAs are differentially expressed compared to women without PCOS, suggesting a role for miRNAs in PCOS pathophysiology. Exercise training modulates miRNA abundance and is primary lifestyle intervention for women with PCOS. Accordingly, we measured the expression of eight circulating miRNAs selected a priori along with miRNA expression from gluteal and abdominal adipose tissue (AT) in 12 women with PCOS and 12 women matched for age and body mass index without PCOS. We also determined the miRNA expression “signatures” before and after high-intensity interval training (HIT) in 42 women with PCOS randomized to either: (1) low-volume HIT (LV-HIT, 10 × 1 min work bouts at maximal, sustainable intensity, n = 13); (2) high-volume HIT (HV-HIT, 4 × 4 min work bouts reaching 90–95% of maximal heart rate, n = 14); or (3) non-exercise control (Non-Ex, n = 15). Both HIT groups trained three times/week for 16 weeks. miRNAs were extracted from plasma, gluteal and abdominal AT, and quantified via a customized plate array containing eight miRNAs associated with PCOS and/or exercise training responses. Basal expression of circulating miRNA-27b (c-miR-27b), implicated in fatty acid metabolism, adipocyte differentiation and inflammation, was 1.8-fold higher in women with compared to without PCOS (P = 0.006) despite no difference in gluteal or abdominal AT miR-27b expression. Only the HV-HIT protocol increased peak oxygen uptake (VO2peak L/min; 9%, P = 0.008). There were no changes in body composition. In LV-HIT, but not HV-HIT, the expression of c-miR-27b decreased (0.5-fold, P = 0.007). None of the remaining seven circulating miRNAs changed in LV-HIT, nor was the expression of gluteal or abdominal AT miRNAs altered. Despite increased cardiorespiratory fitness, HV-HIT did not alter the expression of any circulating, gluteal or abdominal AT miRNAs. We conclude that women with PCOS have a higher basal expression of c-miR-27b compared to women without PCOS and that 16 weeks of LV-HIT reduces the expression of this miRNA in women with PCOS. Intense exercise training had little effect on the abundance of the selected miRNAs within subcutaneous AT depots in women with PCOS. Copyright © 2020 Lionett, Kiel, Camera, Vanky, Parr, Lydersen, Hawley and Moholdt. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Summary Objective Intensive lifestyle interventions (ILI) are criticised for ineffective obesity treatment because weight loss over time is modest and thus of limited clinical relevance. However, a subgroup (5–30%) maintains a clinical weight loss >10%, but it is not clear if cardiometabolic health follows this pattern. The aim was to study the effect of different magnitudes of weight loss maintenance after ILI on cardiometabolic health. Methods Eighty out of 2420 former participants (age: 36 ± 1, BMI: 38 ± 1, (means ±SE)) in an 11–12-week ILI were recruited into 3 groups; clinical weight loss maintenance (>10% weight loss), moderate maintenance (1–10%), and weight regain based on weight loss at follow-up (5.3 ± 0.4 years). Weight loss during the ILI was achieved by increased physical activity and hypo-caloric diet. Dual X-ray Absorptiometry, blood sample, skeletal muscle biopsy and VO 2max test were used to determine cardiometabolic health at follow-up. Results At follow-up, the clinical weight loss maintenance group scored better in the following variables compared to the other groups: BMI (31 ± 1, 33 ± 2, 43 ± 2 kg/m 2 ), composition (34 ± 2, 40 ± 1, 49 ± 1% fat), visceral adipose tissue (0.8 ± 0.2, 1.7 ± 0.5, 2.4 ± 0.4 kg), plasma triglycerides (0.8 ± 0.2, 1.3 ± 0.4, 1.6 ± 0.3 mmol/L), plasma glucose (4.9 ± 0.1, 5.9 ± 0.4, 5.9 ± 0.1 mmol/L), Hb1Ac (5.1 ± 0.0, 5.6 ± 0.2, 5.8 ± 0.2%), protein content in skeletal muscle of GLUT4 (1.5 ± 0.2, 0.9 ± 0.1, 1.0 ± 0.1 AU) and hexokinase II (1.6 ± 0.2, 1.0 ± 0.2, 0.7 ± 0.1 AU), citrate synthase activity (155 ± 6, 130 ± 5, 113 ± 5 μmol/g/min) and VO 2max (49 ± 1, 43 ± 1, 41 ± 1 mL/min/FFM) (p Conclusion Cardiometabolic health is better in participants who have maintained >10% weight loss compared to moderate weight loss and weight regain.